Glycol phosphatides and the preparation thereof from cephalin

ABSTRACT

Glycol phosphatides of the formula   WHEREIN R1 and R2 each are fatty acid groups of 10-24 carbon atoms, inclusive, X is a hydrogen atom or -COOH, which are useful as emulsifiers for intravenous fat-feeding, are produced by removing the amino group of colamine and serine phosphatides by treatment with aqueous nitrous acid under mild conditions followed by diazotization.

United States Patent Betzing 1 Aug. 1, 1972 [54] GLYCOL PHOSPHATIDES AND THE PREPARATION THEREOF FROM CEPHALIN [72] Inventor: Hans Betzing, l-leidestoclt, Germany [73] Assignee: A. Nattermann 8: Cie Gmbll,

Cologne, Braunsfeld, Germany 221 Filed: Sept. 28,1970

211 Appl.No.: 76,231

UNITED STATES PATENTS 3,532,724 10/1970 Smeby et a1. ..260l403 3,577,446 5/1971 Rakhet ..260/403 Primary Examiner-Elbert L. Roberts Attorney-Millen, Raptes & White ABSTRACT Glycol phosphatides of the formula rnc-o-n.

H -O--R2 wherein R and R, each are fatty acid groups of 10-24 carbon atoms, inclusive, X is a hydrogen atom or -COOl-l, which are useful as emulsifiers for intravenous fat-feeding, are produced by removing the amino group of colamine and serine phosphatides by treatment with aqueous nitrous acid under mild conditions followed by diazotization.

10 Claims, No Drawings GLYCOL PHOSPHATIDES AND THE PREPARATION THERmF FROM CEPHALIN BACKGROUND OF THE INVENTION Known cephalin fractions, when obtained from vegetable substance, contain esentially phosphatidyl colamine, in addition to lecithins. When produced from animal sources, they contain both phosphatidyl colamine and phosphatidyl serine. Thae cephalim exhibit, depending on the specific starting material, varying fatty acid residues generally containing -24 carbon atoms. The cephalin fractions preferred simultaneously therapeutic purposes contain phosphatidyl colamines or phosphatidyl serines which have a high percentage of unsaturated. especially polyunsaturated, fatty acid residues. Due to the strong reactivity of the polyunsaturated fatty acids, the isolation thereof is not simple. They are usually obtained during the extraction of raw phosphatides with lower-alcohols.

The cephalins and phosphatide fractions containing them serve, inter alia, as natural emulsifiers since they possess, in addition to the lipophilic fatty acid residues, the hydraphilic glycerophosphoric acid group and colamine or serine residues. However, the emulsifying effect is relatively low, due to the fact that the free amino group is intramolecularly bound as an inner salt with the phosphoric acid group.

Because of the presence of the unsaturated fatty acids, which are valuable for physical-chemical as well as biological reasons, cephalin-containing phosphatide mixtures are also employed as drugs. However, they must be employed with caution as emulsifiers in intravenous fat-feedings because the cephalins as such are blood clotting activators. Furthermore, it was found that the cephalin-containing phosphatides heretofore employed for intravenous fat nourishment can evoke troublesome side effects, such as fever and chills. It has now been discovered, these side-effects are due primarily to the amino group of the cephalins.

US. Pat. No. 3,301,881 discloses a process wherein cephalin is entirely or partially acylated by treatment of aqueous phosphatide emulsions with organic acid anhydrides, whereby the primary amino group is converted into an acid amide. The resulting phosphatides are more plastic and more readily dispersed in aqueous media.

it has now been found that novel phosphatidyl compounds having enhanced utility as emulsifiers, especially for intravenous fat-feeding, can be produced in a simple manner from phosphatidyl colamines and phosphatidyl serines.

SUMMARY OF THE INVENTION According to this invention, the amino group of phosphatidyl colamines and phosphatidyl serines is removed without splitting off the fatty acid groups or chemically altering the sensitive unsaturated or polyunsaturated fatty acid residues during this process, by treatment with nitrous acid followed by diazotization to produce novel glycol phosphatides which can be represented by the general formula wherein R, and R, each are fatty acid groups of 10-24 carbon atoms, preferably unsaturated or polyunsaturated fatty acid groups, i.e., a group of the formula OOCR wherein R is alkyl, alkenyl, alkadienyl, etc., of nine-23 carbon atoms, inclusive, and X is a hydrogen atomoracarboxyl group (-COOH).

DETAILED DISCUSSION Exanmles of the novel compounds of this invention are those wherein R, and R which can be alike or diffel'em are of the formula C Hg CW, C,,I'I,,, COO, C,,H,,,.,COO or C,,I-l,,,.,COO-'wherein n in each instance is an integer from nine-23, inclusive, preferably those wherein R, and R, are substantially entirely, i.e., at least 90 percent, C,,-C,,, or C -C, fatty acid groups, of which a portion is saturated, a portion monoolefinic, a portion dioletinic and a portion polyolefinic, e.g., caproyloxy, undecenoyloxy, dodecanoyloxy, trideooyloxy, tetradecanoyloxy, palmityloxy, stearyloxy, carnaubyloxy, 9-hendecenoyloxy, oleyloxy, brassidyloxy, 9,l2-octadecadienoyloxy, humoceryloxy and linolenyloxy and X is hydrogen, and each of the above wherein X is -CO0H. Included are compounds wherein both R, and R, are saturated, R, is saturated and R, is unsaturated and vice versa, and both R, and R, are unsaturated.

lfthe starting phosphatidyl colamine or phosphatidyl serine is a single chemical entity, the product of the deamination reaction will also be a single chemical compound, e.g., ba-phosphatidylethylene glycol or L- a-phosphatidylglyceric acid wherein the primary ester group is, e.g., palrnityloxy or stearyloxy and the secondary ester group is oleyloxy, linoleyloxy, or archidonyloxy. However, as shown hereinafter, the natural sources of the starting phosphatidyl colamines and serines are a mixture of phosphatides containing a mixture of saturated and unsaturated fatty acid residues. Therefore, a preferred embodiment of this invention employs such a mixture to produce a mixture of compounds of Formula I.

These novel glycol phosphatides, which can also be called deaminocephalins, are completely soluble in alcohol, in contrast to the cephalins. They also exhibit a substantially water solubility than the phosphatidyl colamines and phosphatidyl serines. Since they do not possess the blood clotting side-effect of the cephalins, the novel glycol phosphatides are particularly well suited for intravenous fat-feeding. They are also efl'ective oil-in-water emulsifiers for the production of fat emulsions and the like. Due to the reactive free hydroxy group, the glycol phosphatides are also useful as intermediates for the production of corresponding compounds having a substituted OHgroup, for example, ester compounds, and thus are also valuable intermediates for novel drugs. As stated above, the composition of the fatty acids varies, depending on the starting cephalin employed. In general, the fatty acids having l6 and 18 carbon atoms are predominant,

which is also true of the unsaturated fatty acids. In the case of cephalins from egg yolk, the glycol phosphatides produced therefrom contain, inter alia, C,,,- and C -fatty acids. When using brain as the source of the starting substance, they additionally contain C -fatty acids.

This invention also relates to a process for the preparation of the novel glycol phosphatides of Formula I. They can readily be prepared by dissolving the phosphatidyl colamine or the phosphatidyl serine of the formula O// OH I 11 wherein R R, and X have the values given above, in an organic solvent; mixing the solution with aqueous nitrous acid; and then deaminating the resulting phosphatide compound by diazotization and hydrolysis. The resulting product can be isolated in a conventional manner.

The reaction with nitrous acid should be conducted under mild conditions, for example, by conducting the reaction with cooling. The polyunsaturated fatty acid residues of the phosphatidyl compounds are thus not chemically altered. Investigations by spectral analysis and gas chromatography showed that the characteristic lR-band of cephalin at 9.8 p. disappears,'without the double bonds having been affected by the treatment.

Preferably, the nitrous acid is allowed to react with the cephalins by adding an aqueous solution of a salt of nitrous acid and of an acidic salt of an organic or inorganic acid, dropwise to the cephalin-containing organic solution under agitation. This gentle manner of treating with nitrous acid permits the reaction to be conducted at room temperature or with slight heating, without danger of affecting the steric form of the unsaturated fatty acid residues.

Suitable solvents for the cephalin-containing starting substances include alcohols and chlorinated hydrocarbons of one to four carbon atoms. Hydrocarbon solvents are also suitable. Chloroforrn proved to be especially suitable as a very advantageous solvent for conducting the dearnination reaction.

The deamination process of this invention makes it possible to readily isolate the glycol phosphatides, since their high alcohol solubility facilitates their extraction and separation from accompanying phosphatides.

As an example of a method of conducting the process of this invention, a pure cephalin obtained, for example, by column chromatographical separation of cephalin-rich phosphatide fractions on silica gel columns by elution with chloroform-methanol mixtures, or a cephalin-containing phosphatide mixture, which can contain oil or be de-oiled, is dissolved in an alcohol or a chlorinated hydrocarbon of one to four carbon atoms, in a hydrocarbon solvent, e.g., petroleum ether, hexane, cyclohexane, benzene, etc., or a mixture of these solvents. This solution is then mixed, with cooling, at room temperature or slightly higher temperature, with an aqueous solution of nitrous acid, or successively or simultaneously with an aqueous solution of an alkali or alkaline earth salt of nitrous acid and an acidic salt of an inorganic or organic acid, preferably sodium dihydrogen phosphate, sodium hydrogen citrate, or potassium hydrogen phthalate, and agitated in the absence of air until the free amino group associated with the cephalin phosphatides can no longer be detected with ninhydrin reagent. Thereafter, when employing alcohol, the solvent is entirely or partially evaporated under vacuum and preferably replaced by a chlorinated hydrocarbon. In order to remove the water-soluble components from the organic components, it s also possible to wash the solution two to three times with water. After evaporating the solvent under nitrogen, a yellow to yellowish brown, plastic product results.

The special advantage of the embodiment of the process which employs salt solutions is the fact it is possible to do without acid during the diazotization of the free amino group, and to control the liberation of nitrous acid from the nitrite by means of acidic salts in situ in such a manner that rearrangement of the fatty acids present in the phosphatides into transfatty acids is, for all practical purposes, eliminated. Moreover, there is no change in the fatty acid composition of the reaction products. in particular, the polyunsaturated fatty acid content, specifically polyene-fatty acid content, with their important properties, remains unchanged in the process. is yellowish-brown,

Normally, diazotization is conducted until the quantitative removal of the primary NIL-group of cephalin is accomplished. However, it is also readily possible to operate with smaller quantities of sodium nitrite and acidic salt than employed in the examples, thus obtaining only a partial removal of the amino group from the cephalin molecule, which nevertheless results in phosphatide products which readily disperse in aqueous media.

A further advantage of the process of this invention is the fact that the cephalin-free products exhibit advantageous properties, for example, markedly better acid numbers and phosphorous values than the corresponding starting compounds, as can be seen from Table l below.

TABLE I Compound iodine Acid i: Phos Number Number phorus Commercial cmde phosphatide 86.5 20.3 2.l

Deaminated product of this invention 87.2 9.4 2.34 De-oiled raw phosphatide 70.3 30.] EM

Deaminated product of this invention 77.4 5.5 3.28 Alcohol-insoluble soya phosphatide fraction 66.7 32.2 3.0

Deaminated product of this invention 70.2 l4.4 3.23 Alcohol-soluble soya phosphatide fraction 85.0 l8.0 3.1

Deaminated product of this invention 86.7 4.0 312 in the reaction with nitrous acid according to the process of this invention, pure cephalin compounds can be employed, or phosphatide mixtures containing them. The lecithins still present therein do not interfere with the reaction, for they are not attacked by the nitrous acid under the gentle reaction conditions, since they do not contain any primary amino groups.

[n the investigation of the novel glycol phosphatides obtained in accordance with the process of this invention by deaminating phosphatidyl colamine, the following fatty acids were detected by gas chromatography analysis of the deamination product of soya phosphatides.

TABLE 11 Fatty Acid Composition of Phosphatidyl Glycol Obtained from Soya Phosphatide c,, 0.1% c 0.2% c,, 26.0% is 2.0% c,,1 7.0% c,.,2 60.0% c 4.5% (3,, 0.2%

In this table and also in table ill the subscript numbers are the number of carbon atoms in the fatty acid residue and the superscript numbers, the number of double bonds.

The following fatty acid composition was determined after deamination of a mixture of phosphatidyl colamine and phosphatidyl serine obtained from eggs.

TABLE III Fatty Acid Composition of the Glycol Phosphatide from Egg Cephalin (Mixture of Colamine and Serine Cephalin) Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

EXAMPLE 1 Two hundred g. of pure cephalin (phosphatidyl colamine), produced from an alcohol-insoluble soya phosphatide fraction by separation by column chromatography on silica gel with chloroform-methanol 80 as the eluting agent, is dissolved in a mixture of 1,000 mi. of chloroform and 1,000 ml. of methanol and then mixed, under agitation and in an N, atmosphere, with a solution of 125 g. of sodium nitrite in 200 ml. of distilled water. The mixture is heated in a water bath to 37 C. Then, a solution of 230 g. sodium dihydrogen phosphate 2 H O in 200 ml. of distilled water is gradually added dropwise to the reaction mixture. After a total of 2 hours of agitation at 37 C., all of the cephalin has been diazotized, and no amino group, i.e. no cephalin, can be detected by thin-layer chromatography with ninhydrin reagent.

In order to work up the reaction mixture, the solvent is decanted from the insoluble material which, after washing with a small amount of chloroform, is

discarded. The combined chloroform solutions are transferred into a separating funnel and, if necessary, mixed with an amount of water such that two layers are formed. The lower, chloroform-containing layer is separated and washed with about 400 ml. of water and then again separated from the aqueous phase in a separating funnel. After evaporating the solvent under vacuum and N,, 190 g. of glycol phosphatide remains of Formula I in which R, and R, are fatty acid groups of the composition shown in Table II and X is Hydrogen.

EXAMPLE 2 Five hundred g. of the alcohol-insoluble soya phosphatide fraction, as it is obtained as the residue by de-oiling commercial soya phosphatide with acetone and subsequent repeated extraction of the de-oiled product with ethanol under heating, (cephalin content about 30 percent), is dissolved in a mixture of 700 ml. of chloroform and 500 ml. of methanol under agitation and introduction of N and then mixed with a solution of 69 g. of NaNO, in ml. of distilled water. To this mixture is added dropwise, under agitation, a solution of B8 g. of Nal-LPO, H,O in ml. of distilled water, whereupon the reaction mixture is further agitated at room temperature under N After 3.5 hours, a sample of the substance, after separation by thin-layer chromatography on silica gel G-plates, using chloroform-methanol-water (65:25: as the eluent, is tested with ninhydrin reagent and shows no cephalin in the mixture. The solution is decanted off from the thusseparated, semi-solid phosphate and mixed with distilled water until two layers have formed. For this purpose, about ml. of water is required. The aqueous phase (upper phase) is separated in separating funnels and discarded. After the addition of about 200 ml. of water, the mixture is thoroughly mixed and again separated from the aqueous phase. If the second aqueous phase is still markedly acidic, the reaction solution is once more washed with water. After removing the solvent under vacuum by evaporation under an N, atmosphere, 400 g. of a phosphatide mixture is obtained from the chloroform phase (iodine number 70', acid number l4; P 3.2 percent) which contains, in place of cephalin, a glycol phosphatide of this invention corresponding to Formula I in which R, and R, are fatty acid groups and X in a portion thereof is H and in the remainder is -COOH.

The following experiment demonstrates the improved emulsion-fomting capability of this product:

One gram of the phosphatide mixture containing the above described glycol phosphatide is dissolved, by agitation and heating to 6070 C., in 10 g. of sunflower oil. After cooling to 20 C., the mixture is transferred into a 100 ml. shaker cylinder and 90 ml. of distilled water of 20C. is added. By a vigorous rotation of the cylinder 90 every 30 seconds, the two phases are emulsified. The number of rotations required to obtain an emulsion stable for 30 seconds are measured. For the cephalin-free product, only two rotations are necessary whereas when employing the starting material, ie the cephalin-containing, alcohol-insoluble phosphatide fraction in the same test no emulsion is obtained, even after 50 rotations.

Two kg. of crude soya phosphatide, freed of oil by repeated treatment with acetone, is dissolved in a mixture of 4 liters of chloroform and 1 liter of methanol under agitation and under an inert gas 2), and then mixed with a solution of 250 g. of NaNO, in 220 ml. of warm distilled water. The reaction mixture is heated to 50 C. and a solution of 460 g. of NaI-LPO, 1 H O in 450 ml. of warm distilled water is added dropwise thereto and mixed therewith. After a total of 2 hours of agitation at 50 C. under N the reaction product is free of cephalin. After cooling to room temperature, the chloroform-methanol solution is decanted off from the inorganic residue, the residue is washed out with a small amount of chloroform, which is added to the decanted solution. The combined solutions are then stirred with 500 ml. of water under a nitrogen atmosphere, the solution is allowed to settle briefly in a separating funnel and then the lower chloroform layer is separated from the wash water. The chloroform solution is then again washed out twice with 400 ml. portions of water. Finally, the chloroform solution is freed of solvent under vacuum and N There remains 1.8 kg. (90 percent) of a yellowish-brown, plastic phosphatide mixture exhibiting the following characteristics: iodine number= 78', acid number 5.5; P 3.3 percent.

In the emulsion forming test described in Example 2, a stable emulsion is obtained after one rotation, compared to 16 rotations required for the starting material.

EXAMPLE 4 One kg. of an alcohol-soluble phosphatide fraction, obtained by de-oiling commercial crude phosphatides with acetone and subsequent repeated extraction of the de-oiled phosphatide mixture with alcohol, is dissolved in 3 liters of ethanol and mixed, under agitation and an atmosphere of N,, with a solution of 120 g. of NaNO, in 120 ml. of water and a solution of 200 g. of Nal-IJ'O, 1 H in 200 ml. of water. Both salts are dissolved with heating in distilled water. The reaction mixture is warmed to 50" C. under agitation and an atmosphere of N After about 1 hours, the cephalin has been completely diazotized. The reaction solution is decanted off from the residue, and the residue is washed with a small amount of ethanol, which is mixed with the reaction solution. By distillation under vacuum and N the alcohol is distilled off up to about 700 ml. and about [.5 liters of chloroform is added to the residue. The solution is washed out two to three times with about 300 ml. portions of water and the washing water is discarded. The chloroform solution is evaporated under a vacuum and a nitrogen atmosphere. There remains 950 g. (95 percent) of the cephalin-free mixture containing a glycol phosphatide exhibiting the following characteristics: iodine number 82; acid number 4; P 3.2 percent.

EXAMPLE 5 One kilogram of commercial crude soya phosphatide is dissolved in 1.2 liters of dichloroethane and 600 ml. of ethanol under a protective N, atmosphere and, under agitation at a temperature of 50 C., is then mixed successively with a solution of 100 g. of NaNO, in 120 ml. of water and 170 g. of Nal-l P0 1 H O in 175 ml. of water. It is advantageous to add the sodium hydrogen phosphate solution gradually dropwise. After agitating for 2.5 hours, the reaction mixture is free of cephalin. Afier cooling to room temperature. the solution is decanted, the semi-solid residue is washed with dichloroethane, the washing liquid is added to the primary solution, and the dichloroethane-ethanol solution is washed two to three times with about 250 ml. portions of water. After the solvent has been distilled off under a vacuum and N 950 g. of an oil-containing, cephalin-free crude phosphatide remains.

in order to obtain a stable emulsion in the test described in Example 2, only 1 rotation is necessary compared to l0 rotations in case of the starting commercial crude phosphatide.

EXAMPLE 6 One kg. of the same alcohol-insoluble soya phosphatide fraction as employed in Example 2 is dissolved, under agitation and a protective inert gas atmosphere, in 2 liters of hexane and, after heating to 50 C., is mixed with a solution of 200 g. of sodium nitrite in 325 ml. of water. To the reaction mixture is added dropwise a solution of 400 g. of sodium dihydrogen phosphate in 550 ml. of water. After a total of 2.5 hours of intensive agitation, the phosphatide fraction is cephalin-free. The reaction mixture is suitably allowed to cool in a refrigerator, and then the solution which forms at the top is decanted. The residue is repeatedly washed with hexane. The hexane solutions are combined and then shaken out about three times with 300 ml. portions of water. The aqueous phases are separated, if necessary by brief centrifugation, and discarded. The hexane solutions are freed of the solvent under vacuum, leaving 750 g. of a phosphatide mixture containing, in place of cephalin, a glycol phosphatide of this invention.

EXAMPLE 7 Five hundred g. of an alcohol-soluble phosphatide fraction, obtained in accordance with the process of German Patent No. 1,047,597, is dissolved in a mixture of 700 ml. of chloroform and 500 ml. of methanol and mixed, under agitation and heating to 50 C., successively with a solution of g. of sodium nitrite in 200 ml. of water and a slurry of 185 g. of potassium hydrogen phthalate in ml. of water. After 7 hours, the reaction mixture is free of cephalin. After cooling, the solution formed on top is decanted from the insoluble substance, which is then washed with chloroform. The washing liquor is combined with the chloroformmethanol solution and washed repeatedly with about ml. of water. Then, the chloroform solution is evaporated under vacuum and nitrogen. Yield: 450 g. of an alcohol-soluble phosphatide mixture containing a glycol phosphatide of this invention.

EXAMPLE8 One hundred and eighty g. of crude egg phosphatide, produced from fresh egg yolk by treatment with acetone to remove the neutral lipids and the cholesterol, and then by extraction of the oil-free residue with chloroform-methanol (2:1) and washing out the water-soluble components according to the procedure of J. Folch and co-worker (J. Biol. Chem.

191, 833, i951), containing serine phosphatide as well as colamine phosphatide, is dissolved in a mixture of 1 liter of chloroform and 1 liter of methanol, and mixed, under agitation and heating to 37 C., successively with a solution of 120 g. of sodium dihydrogen phosphate and 60 g. of sodium nitrite, each in 200 ml. of water. After agitation for 3.5 hours, the reaction product is free of ninhydrin-positive phosphatides. The chloroform-containing solution is separated from the thus-formed aqueous phase and shaken out one to two times with 200 ml. portions of water. After distilling off the solvent under vacuum and N there remains 169 g. of a cephalin-free phosphatide mixture containing the corresponding glycol phosphatides in which the fatty acid groups correspond to the composition shown in table ll.

EXAMPLE 9 Five hundred g. of an alcohol-soluble phosphatide fraction, obtained as described in Example 4, is dissolved in 1.5 liters of ethanol and mixed at room temperature with an aqueous solution of nitrous acid cooled to C., produced by adding dropwise, under ice cooling, 470 ml. of 12.5 percent hydrochloric acid to 200 g. of sodium nitrite dissolved in a mixture of 800 ml. of water and 250 ml. of ethanol. Afier agitating for three hours under a protective nitrogen atmosphere, the phosphatide mixture no longer exhibits any reaction to ninhydrin reagent. By adding chloroform, two layers are formed, of which the lower layer is separated and washed with water. After evaporating the solvent under vacuum and a protective nitrogen atmosphere, 470 g. of a mixture containing glycol phosphatide is obtained.

The preceding examples can be repeated with similar success by substituting the generically or specifically described reactants and/or operating conditions of this invention for those used in the preceding examples.

From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

What is claimed is:

l. A glycol phosphatide of the formula wherein R, and R, each are fatty acid groups of 10-24 carbon atoms, inclusive, and X is a hydrogen atom or -COOH.

2. A compound of claim 1, wherein X is H.

3. A compound of claim 1, wherein X is -COOH.

4. A compound of claim 1, wherein R and R, are substantially entirely C -C fatty acid groups.

5. A compound of claim 1, wherein R, and R, are substantially entirely C -C fatty acid groups.

6. A process for the production of glycol phosphatides according to Claim 1, which comprises diazotization of one or both of a phosphatidyl colamine or phosphatidyl serine of the formula wherein R,, R, and X have the values given therein, with nitrous acid followed by hydrolysis of the resulting diazotized product with an acidic salt of an organic or inorganic acid.

7. A process according to claim 6, which comprises mixing a solution of the starting phosphatidyl compound in an organic solvent with an aqueous solution of a salt of nitrous acid and sodium dihydrogen phosphate, sodium hydrogen citrate or potassium hydrogen phthalate.

8. A process according to claim 7, wherein there is added to a solution of the starting phosphatidyl compound an aqueous solution of sodium nitrite and sodium dihydrogen phosphate.

9. A process according to claim 6, wherein the diazotization and hydrolysis reactions are conducted in an alcohol, a chlorinated hydrocarbon of one to four carbon atoms, a hydrocarbon solvent, or a mixture thereof.

10. A process according to claim 9, wherein the reaction solvent is chloroform. 

2. A compound of claim 1, wherein X is H.
 3. A compound of claim 1, wherein X is -COOH.
 4. A compound of claim 1, wherein R1 and R2 are substantially entirely C16-C20 fatty acid groups.
 5. A compound of claim 1, wherein R1 and R2 are substantially entirely C16-C18 fatty acid groups.
 6. A process for the production of glycol phosphatides according to Claim 1, which comprises diazotization of one or both of a phosphatidyl colamine or phosphatidyl serine of the formula
 7. A process according to claim 6, which comprises mixing a solution of the starting phosphatidyl compound in an organic solvent with an aqueous solution of a salt of nitrous acid and sodium dihydrogen phosphate, sodium hydrogen citrate or potassium hydrogen phthalate.
 8. A process according to claim 7, wherein there is added to a solution of the starting phosphatidyl compound an aqueous solution of sodium nitrite and sodium dihydrogen phosphate.
 9. A process according to claim 6, wherein the diazotization and hydrolysis reactions are conducted in an alcohol, a chlorinated hydrocarbon of one to four carbon atoms, a hydrocarbon solvent, or a mixture thereof.
 10. A process according to claim 9, wherein the reaction solvent is chloroform. 